Multitask Adversarial Networks Based on Extensive Nonlinear Spiking Neuron Models.

Deep learning technology has been successfully used in Chest X-ray (CXR) images of COVID-19 patients. However, due to the characteristics of COVID-19 pneumonia and X-ray imaging, the deep learning methods still face many challenges, such as lower imaging quality, fewer training samples, complex radiological features and irregular shapes. To address these challenges, this study first introduces an extensive NSNP-like neuron model, and then proposes a multitask adversarial network architecture based on ENSNP-like neurons for chest X-ray images of COVID-19, called MAE-Net. The MAE-Net serves two tasks: (i) converting low-quality CXR images to high-quality images; (ii) classifying CXR images of COVID-19. The adversarial architecture of MAE-Net uses two generators and two discriminators, and two new loss functions have been introduced to guide the optimization of the network. The MAE-Net is tested on four benchmark COVID-19 CXR image datasets and compared them with eight deep learning models. The experimental results show that the proposed MAE-Net can enhance the conversion quality and the accuracy of image classification results.

Multi-omics characterization of esophageal squamous cell carcinoma identifies molecular subtypes and therapeutic targets.

Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer and is characterized by an unfavorable prognosis. To elucidate the distinct molecular alterations in ESCC and investigate therapeutic targets, we performed a comprehensive analysis of transcriptomic, proteomic, and phosphoproteomic data derived from 60 paired treatment-naive ESCC and adjacent non-tumor tissue samples. Additionally, we conducted a correlation analysis to describe the regulatory relationship between transcriptomic and proteomic processes, revealing alterations in key metabolic pathways. Unsupervised clustering analysis of the proteomic data stratified ESCC patients into three subtypes with different molecular characteristics and clinical outcomes. Notably, subtype III exhibited the worst prognosis and enrichment in proteins associated with malignant processes, including glycolysis and DNA repair pathways. Furthermore, translocase of inner mitochondrial membrane domain containing 1 (TIMMDC1) was validated as a potential prognostic molecule for ESCC. Moreover, integrated kinase-substrate network analysis using the phosphoproteome nominated candidate kinases as potential targets. In vitro and in vivo experiments further confirmed casein kinase II subunit alpha (CSNK2A1) as a potential kinase target for ESCC. These underlying data represent a valuable resource for researchers, which may provide better insights into the biology and treatment of ESCC.

Multiple-in-Single-Out Object Detector Leveraging Spiking Neural Membrane Systems and Multiple Transformers.

Most existing multi-scale object detectors depend on multi-level feature maps. The Feature Pyramid Networks (FPN) is a significant architecture for object detection that utilizes these multi-level feature maps. However, the use of FPN also increases the detector's complexity. For object detection methods that only use a single-level feature map, the detection performance is limited to some extent because the single-level feature map cannot balance deep semantic information and shallow detail information. We introduce a novel detector - the Spiking Neural P Multiple-in-Single-out (SNPMiSo) detector to address these challenges. The SNPMiSo detector is constructed based on SNP-like neurons. In SNPMiSo, we employ two kinds of Transformers to boost the important features across different-level feature maps separately. After enhancing the features, we use an incremental upsampling module to upsample and merge the two feature maps. This combined feature map is input into the NAF dilated residual module and the NAF dual-branch detection head. This process allows us to extract multi-scale features and carry out detection tasks. Our tests show promising results: On the COCO dataset, SNPMiSo attains an Average Precision (AP) of 38.7, an improvement of 1.0 AP over YOLOF. In addition, SNPMiSo demonstrates a quicker detection speed, outperforming some advanced multi-level and single-level object detectors.

A Parallel Convolutional Network Based on Spiking Neural Systems.

Deep convolutional neural networks have shown advanced performance in accurately segmenting images. In this paper, an SNP-like convolutional neuron structure is introduced, abstracted from the nonlinear mechanism in nonlinear spiking neural P (NSNP) systems. Then, a U-shaped convolutional neural network named SNP-like parallel-convolutional network, or SPC-Net, is constructed for segmentation tasks. The dual-convolution concatenate (DCC) and dual-convolution addition (DCA) network blocks are designed, respectively, in the encoder and decoder stages. The two blocks employ parallel convolution with different kernel sizes to improve feature representation ability and make full use of spatial detail information. Meanwhile, different feature fusion strategies are used to fuse their features to achieve feature complementarity and augmentation. Furthermore, a dual-scale pooling (DSP) module in the bottleneck is designed to improve the feature extraction capability, which can extract multi-scale contextual information and reduce information loss while extracting salient features. The SPC-Net is applied in medical image segmentation tasks and is compared with several recent segmentation methods on the GlaS and CRAG datasets. The proposed SPC-Net achieves 90.77% DICE coefficient, 83.76% IoU score and 83.93% F1 score, 86.33% ObjDice coefficient, 135.60 Obj-Hausdorff distance, respectively. The experimental results show that the proposed model can achieve good segmentation performance.

A Prediction Model Based on Gated Nonlinear Spiking Neural Systems.

Nonlinear spiking neural P (NSNP) systems are one of neural-like membrane computing models, abstracted by nonlinear spiking mechanisms of biological neurons. NSNP systems have a nonlinear structure and can show rich nonlinear dynamics. In this paper, we introduce a variant of NSNP systems, called gated nonlinear spiking neural P systems or GNSNP systems. Based on GNSNP systems, a recurrent-like model is investigated, called GNSNP model. Moreover, exchange rate forecasting tasks are used as the application background to verify its ability. For the purpose, we develop a prediction model based on GNSNP model, called ERF-GNSNP model. In ERF-GNSNP model, the GNSNP model is followed by a "dense" layer, which is used to capture the correlation between different sub-series in multivariate time series. To evaluate the prediction performance, nine groups of exchange rate data sets are utilized to compare the proposed ERF-GNSNP model with 25 baseline prediction models. The comparison results demonstrate the effectiveness of the proposed ERF-GNSNP model for exchange rate forecasting tasks.

[Retracted] miRNA­1207­5p is associated with cancer progression by targeting stomatin­like protein 2 in esophageal carcinoma.

Subsequently to the publication of the above article, and a Corrigendum that has already been published with the intention of showing corrected versions of Figs. 3 and 6 (DOI: 10.3892/ijo.2018.4254; published online on January 24, 2018), a concerned reader drew to the Editor's attention that there appeared to be an unexpected overlap of data in a couple of the panels showing flow cytometric data in Fig. 3A; furthermore, strikingly similar data also appeared in a paper that was submitted to the journal Cancer Gene Therapy at around the same time [Zang W, Wang T, Huang J, Li M, Wang Y, Du Y, Chen X and Zhao G: Long noncoding RNA PEG10 regulates proliferation and invasion of esophageal cancer cells. Cancer Gene Ther 22: 138­144, 2015]. Considering the latest discrepancies and concerns that have been raised with another of the figures in this paper, the Editor of International Journal of Oncology has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership of the Journal for any inconvenience caused. [International Journal of Oncology 46: 2163­2171, 2015; DOI: 10.3892/ijo.2015.2900].

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

[Corrigendum] miRNA-1207-5p is associated with cancer progression by targeting stomatin-like protein 2 in esophageal carcinoma.

An interested reader drew to our attention that, in the above-mentioned article, there were two figures where identity in certain of the data was shared between panels within the same figure. First, in Fig. 3B, the data shown for the EC9706 cell line/negative control (NC) experiment were derived from the same original source as those for the EC-1/Blank control experiment. Secondly, in Fig. 6B the Bcl-2 bands for the two different cell lines, EC9706 and EC-1, were inadvertently duplicated (the data shown for the EC9706 cell line were correct). We have reviewed the original files and the individual figures for the submitted composite figures, and realize that the errors occurred when we produced the composite figures. The same images were accidentally inserted twice in Figs. 3 and 6 without us being fully aware of the error. We have identified all the original images, and the corrected versions of Figs. 3 and 6 are shown opposite. We regret that these errors went unnoticed prior to publication, and thank the Editor for affording us the opportunity to publish this Corrigendum. We also regret any inconvenience caused to the readership of the journal. [the original article was published in the International Journal of Oncology 46: 2163-2171, 2015; DOI: 10.3892/ijo.2015.2900].

A Lightweight Anonymous Authentication Protocol with Perfect Forward Secrecy for Wireless Sensor Networks.

Due to their frequent use in unattended and hostile deployment environments, the security in wireless sensor networks (WSNs) has attracted much interest in the past two decades. However, it remains a challenge to design a lightweight authentication protocol for WSNs because the designers are confronted with a series of desirable security requirements, e.g., user anonymity, perfect forward secrecy, resistance to de-synchronization attack. Recently, the authors presented two authentication schemes that attempt to provide user anonymity and to resist various known attacks. Unfortunately, in this work we shall show that user anonymity of the two schemes is achieved at the price of an impractical search operation-the gateway node may search for every possible value. Besides this defect, they are also prone to smart card loss attacks and have no provision for perfect forward secrecy. As our main contribution, a lightweight anonymous authentication scheme with perfect forward secrecy is designed, and what we believe the most interesting feature is that user anonymity, perfect forward secrecy, and resistance to de-synchronization attack can be achieved at the same time. As far as we know, it is extremely difficult to meet these security features simultaneously only using the lightweight operations, such as symmetric encryption/decryption and hash functions.

[Cost-effectiveness analysis of esophageal cancer once-in-a-lifetime endoscopic screening in high-risk areas of rural China].

OBJECTIVE: To estimate the cost-effectiveness of esophageal cancer endoscopic screening once-in-a-lifetime and to predict the optimal screening age for people in high-risk areas of rural China. METHODS: A Markov model was constructed to predict and compare the effect of four esophageal cancer endoscopic screening modalities which varied with different screening ages. Long-term epidemiological effectiveness and cost-effectiveness were predicted by simulation of the model. RESULTS: Compared with the control group, strategies starting at 40, 45, 50 and 55 year-old had saved life-years of 629.51, 769.88, 738.98 and 533.21 years per 100 000 people, respectively, of which the strategy starting at 45 year-old saved the maximum life years. All strategies were cost-effective and starting at 40 year-old cost the most per life-year saved. Among all alternatives, strategies starting age at 45 year-old and 50 year-old were incremental cost-effective, and the incremental cost-effective ratios were 34 962.87 and 3 346.43 RMB per life year saved, respectively. CONCLUSIONS: The strategy starting at 40 year-old implemented at present and other strategies were cost-effective in high-risk areas of rural China. However, the 45-year-old group is more aligned with the principle of cost-effectiveness. Considering the cost-effectiveness of different strategies and social economic status, 45 year-old is regarded as the optimal starting age of esophageal cancer once-in-a-lifetime endoscopic screening and is recommended in areas lacking health resources. The strategy of starting age at 40 year-old which could obtain better screening effects would be preferable in wealthy regions.

miRNA-1207-5p is associated with cancer progression by targeting stomatin-like protein 2 in esophageal carcinoma.

Newly discovered intrinsic regulators, the miRNAs regulate gene expression by binding to the 3'-untranslated regions of the genome. Accumulating studies have indicated that miRNAs are aberrantly expressed in various human cancers. We found that miRNA-1207-5p (miR­1207-5p) was markedly downregulated in esophageal carcinoma (EC) tissues, and was correlated with EC differentiation, pathological stage and lymph node metastasis. Rates of apoptosis were increased and cell invasion ability was decreased in EC9706 and EC-1 cells transfected with a miR­1207-5p mimic. Stomatin-like protein 2 (STOML-2) was predicted to be a potential target of miR­1207-5p by bioinformatics analysis and this was confirmed by luciferase assay and western blotting. Our study showed that STOML-2 was negatively regulated by miR­1207-5p. Furthermore, overexpression of STOML-2 abolished the miR­1207-5p anti-invasion function. Based on these results, we proposed that miR­1207-5p might act as a potential therapeutic target in the treatment of EC.

Upregulation of miR-494 Inhibits Cell Growth and Invasion and Induces Cell Apoptosis by Targeting Cleft Lip and Palate Transmembrane 1-Like in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Potential target genes of microRNA (miR)-494 have been reported in many types of cancers. However, the role of miR-494 in esophageal squamous cell carcinoma (ESCC) remains unknown. AIM: This study focused on the expression and biological function of miR-494 in ESCC. METHODS: Using bioinformatics analyses, we found that cleft lip and palate transmembrane 1-like (CLPTM1L) was a potential target of miR-494. We performed quantitative real-time (qRT) PCR assays in 37 ESCC tumor tissues to determine the expression of miR-494 and CLPTM1L mRNA, and we analyzed the correlation between both of these factors and clinical characteristics. The cell counting kit-8 and colony formation assays were used to evaluate the effects of miR-494 expression on the proliferation of ESCC cells. The transwell migration assay and flow cytometric apoptosis assay were performed to study the influence of miR-494 on the invasion and apoptosis of ESCC cells. Western blotting, luciferase assays, and CLPTM1L knockdown experiments were used to determine whether CLPTM1L was a target of miR-494. RESULTS: The qRT-PCR assays showed significant downregulation of miR-494 (P < 0.05) and upregulation of CLPTM1L mRNA (P < 0.05), both of which were significantly associated with lymph node metastases (P < 0.05). High expression of miR-494 inhibited cell proliferation and invasion and promoted cell apoptosis (P < 0.05). The results also showed that CLPTM1L was a target of miR-494. CONCLUSION: These results show that the expression of miR-494, which can regulate cell growth, invasion and apoptosis of ESCC cells by targeting CLPTM1L, is downregulated in ESCC tumor tissues. The miR-494-CLPTM1L pathway could be further exploited to develop a new approach to treat ESCC.

Similarity measure and entropy of fuzzy soft sets.

Soft set theory, proposed by Molodtsov, has been regarded as an effective mathematical tool to deal with uncertainties. Recently, uncertainty measures of soft sets and fuzzy soft sets have gained attentions from researchers. This paper is devoted to the study of uncertainty measures of fuzzy soft sets. The axioms for similarity measure and entropy are proposed. A new category of similarity measures and entropies is presented based on fuzzy equivalence. Our approach is general in the sense that by using different fuzzy equivalences one gets different similarity measures and entropies. The relationships among these measures and the other proposals in the literatures are analyzed.

Esophageal/gastric cancer screening in high-risk populations in Henan Province, China.

OBJECTIVE: To summarize the endoscopic screening findings in high-risk population of esophageal and gastric carcinoma and analyze influential factors related to screening. METHODS: In seven selected cities and counties with high incidences of esophageal carcinoma, people at age of 40-69 were set as the target population. Those with gastroscopy contradictions were excluded, and all who were voluntary and willing to comply with the medical requirements were subjected to endoscopic screening and histological examination for esophageal, gastric cardia and gastric carcinoma in accordance with national technical manual for early detection and treatment of cancer. RESULTS: In three years, 36,154 people were screened, and 16,847 (46.60%) cases were found to have precancerous lesions. A total of 875 cases were found to have cancers (2.42%), and among them 739 cases had early stage with an early diagnosis rate is 84.5%. Some 715 patients underwent prompt treatment and the success rate was 81.8%. CONCLUSIONS: In a high-risk population of esophageal and gastric carcinoma, it is feasible to implement early detection and treatment by endoscopic screening. Screening can identify potential invasive carcinoma, early stage carcinoma and precancerous lesions, improving efficacy through early detection and treatment. The exploratory analysis of related influential factors will help broad implementation of early detection and treatment for esophageal and gastric carcinoma.

[Prediction of temporal trends in gastric cancer mortality in Linzhou city from 1988 to 2010].

OBJECTIVE: To describe the temporal trends in the mortality rate of gastric cancer during the period of 1988 and 2010, and to predict the gastric cancer mortality between 2016 - 2020. METHODS: The data of gastric cancer mortality in Linzhou city between 1988 and 2010 was extracted from the cancer registry, including a total of 11 714 cases, covering 22 447 073 person-years. The mortality rate of gastric cancer of each 5-year period was calculated by sub-site and gender. Age-standardized rate (ASR) was calculated using the Chinese standard population in 1982. Intrinsic estimator (IE) model was used to fit the mortality trend by sub-site and gender, and to predict the mortality of gastric cancer in Linzhou city between 2016 and 2020. RESULTS: From 1988 to 2010, the gastric cancer mortality in Linzhou city was 52.18/100 000 (11 714/22 447 073) with the ASR at 49.23/100 000; the mortality in male was 67.02/100 000 (7678/11 455 512) with ASR at 68.68/100 000 while the mortality in female was 36.72/100 000 (4036/10 991 561) with ASR at 32.12/100 000. The mortality of cardia carcinoma was 27.87/100 000 (6257/22 447 073) with the ASR at 26.37/100 000; while the mortality of non-cardia carcinoma was 24.31/100 000 (5457/22 447 073) with the ASR at 22.86/100 000. The ASR of gastric cancer during 1988 - 1990 was 63.37/100 000 (1653 cases) and decreased by 28.34%, to 45.41/100 000 (2622 cases) during 2006 - 2010. The IE model showed that the birth cohort effect decreased greatly. The mortality risk of cardia carcinoma in population born after 1950s, decreased significantly; and the mortality risk of non-cardia carcinoma in population born in 20 century continually decreased. The death of gastric cancer among the population over 30 years old was predicted to be 3626 cases, increasing by 40.60% compared with the number between 2006 and 2010 (2579 cases). Among them, the mortality of cardia carcinoma increased by 51.89% (predicted number between 2016 and 2020 was 2456 cases, and 1617 cases between 2006 and 2010), and the mortality of non-cardia carcinoma increased by 21.62% (predicted number between 2016 and 2020 was 1170 cases, and 962 cases between 2006 and 2010). CONCLUSION: The mortality rate of gastric cancer in Linzhou city showed a decreasing trend during the period of 1988-2010, being mainly attributed to the cohort effect. However, the mortality will still increase in the future, between 2016 and 2020.

Time trends of esophageal cancer mortality in Linzhou city during the period 1988-2010 and a Bayesian approach projection for 2020.

In recent decades, decreasing trends in esophageal cancer mortality have been observed across China. We here describe esophageal cancer mortality trends in Linzhou city, a high-incidence region of esophageal cancer in China, during 1988-2010 and make a esophageal cancer mortality projection in the period 2011-2020 using a Bayesian approach. Age standardized mortality rates were estimated by direct standardization to the World population structure in 1985. A Bayesian age-period-cohort (BAPC) analysis was carried out in order to investigate the effect of the age, period and birth cohort on esophageal cancer mortality in Linzhou during 1988-2010 and to estimate future trends for the period 2011-2020. Age-adjusted rates for men and women decreased from 1988 to 2005 and changed little thereafter. Risk increased from 30 years of age until the very elderly. Period effects showed little variation in risk throughout 1988-2010. In contrast, a cohort effect showed risk decreased greatly in later cohorts. Forecasting, based on BAPC modeling, resulted in a increasing burden of mortality and a decreasing age standardized mortality rate of esophageal cancer in Linzhou city. The decrease of esophageal cancer mortality risk since the 1930 cohort could be attributable to the improvements of social- economic environment and lifestyle. The standardized mortality rates of esophageal cancer should decrease continually. The effect of aging on the population could explain the increase in esophageal mortality projected for 2020.

Cost-benefit analysis of esophageal cancer endoscopic screening in high-risk areas of China.

AIM: To estimate the cost-benefit of endoscopic screening strategies of esophageal cancer (EC) in high-risk areas of China. METHODS: Markov model-based analyses were conducted to compare the net present values (NPVs) and the benefit-cost ratios (BCRs) of 12 EC endoscopic screening strategies. Strategies varied according to the targeted screening age, screening frequencies, and follow-up intervals. Model parameters were collected from population-based studies in China, published literatures, and surveillance data. RESULTS: Compared with non-screening outcomes, all strategies with hypothetical 100,000 subjects saved life years. Among five dominant strategies determined by the incremental cost-effectiveness analysis, screening once at age 50 years incurred the lowest NPV (international dollar-I$55 million) and BCR (2.52). Screening six times between 40-70 years at a 5-year interval [i.e., six times(40)f-strategy] yielded the highest NPV (I$99 million) and BCR (3.06). Compared with six times(40)f-strategy, screening thrice between 40-70 years at a 10-year interval resulted in relatively lower NPV, but the same BCR. CONCLUSION: EC endoscopic screening is cost-beneficial in high-risk areas of China. Policy-makers should consider the cost-benefit, population acceptance, and local economic status when choosing suitable screening strategies.

Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies.

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.

[Time trends in esophageal cancer mortality in Linzhou city in 1986 - 2010 and future prediction].

OBJECTIVE: To analyze the trends in mortality of esophageal cancer and explore the effects of age, period and cohort on esophageal cancer mortality rate in Linzhou city in 1986 - 2010, and predict the mortality of esophageal cancer in 2016 - 2020. METHODS: All of the esophageal cancer-attributed deaths in 1986 - 2010 were drawn from the database in Center of Cancer and Vita Statistics in Henan Province. The numbers of the death cases and population were tabulated into 5-year age groups and 5-year period groups for each sex and linked each other. The age-adjusted mortality rates were calculated by direct standardization to the Chinese population structure in 1982. Intrinsic estimator model (IE model)was used to perform the age-period-cohort analysis and estimate the corresponding parameters. Age effect, period effect and cohort effect on esophageal cancer mortality rate was plotted separately. The mortality of esophageal cancer during 2016 - 2020 was predicted according to the parameters by that model. RESULTS: A total of 15432 cases died from esophageal cancer in Linzhou city in1986 - 2010. The overall crude mortality rate was 63.89 per 100, 000. Among men, the age-adjusted mortality rate was 109.66 per 100, 000 during 1986-1990 and decreased to 60.59 per 100, 000 during 2006 - 2010. For women, the age-adjusted mortality rate decreased from 74.72 per 100, 000 to 39.05 per 100, 000 at the same two calendar periods. The IE model showed that age effect was remarkable, the period effect was stable and the cohort effect decreased greatly. The predicted mortality of over 30-years old population during 2016 - 2020 is 1501 for men and 1083 for women. Compared with 2006 - 2010 period the mortality will be decreased by 6.71% and 11.08%, respectively. CONCLUSIONS: The mortality rate of esophageal cancer in Linzhou city shows a decreasing trend during the period of 1986 - 2010. This trend is mainly attributed to the cohort effect. The predicted mortality in the future will decrease continually.

Potential role of minichromosome maintenance protein 2 as a screening biomarker in esophageal cancer high-risk population in China.

Minichromosome maintenance proteins are novel proliferative markers that have been proposed as diagnostic markers in many cancers. We evaluated the potential role of minichromosome maintenance protein 2 as a screening biomarker and compared it with proliferating cell nuclear antigen and Ki67 in a population survey of esophageal squamous cell carcinoma. A total of 299 esophageal samples from a high-risk region in China, including 171 from an endoscopy population survey, 30 from brushing cytology, and 98 from surgery and autopsy, underwent immunostaining with minichromosome maintenance protein 2, proliferating cell nuclear antigen, and Ki67 antibodies. Minichromosome maintenance protein 2 expression was confined to the proliferative compartment of normal and abnormal esophageal epithelium and particularly manifested in the surface layer of dysplasia and carcinoma in situ. The expression of proliferating cell nuclear antigen and Ki67 was positively correlated with that of minichromosome maintenance protein 2 (r(s) >0.39, P < .01); but their positive nuclei seldom reached the surface layer, and the labeling indices were significantly lower than those for minichromosome maintenance protein 2 in dysplasia (P < .05) and carcinoma in situ (P < .001). The sensitivity and specificity of minichromosome maintenance protein 2 in diagnosing dysplasia were 91.3% and 61.8%, respectively, higher than those for proliferating cell nuclear antigen (88.4% and 47.1%) and Ki67 (78.3% and 57.8%). Nine of 10 cancer and paracancerous surface-brushing samples expressed minichromosome maintenance protein 2, and the detection was higher than that for proliferating cell nuclear antigen (8/10 and 7/10) and Ki67 (7/10 and 7/10). However, none of 10 normal surface-brushing samples expressed the 3 markers. Minichromosome maintenance protein 2 is more sensitive and specific than proliferating cell nuclear antigen and Ki67 in indicating esophageal dysplasia. Minichromosome maintenance protein 2 immunostaining combined with surface brushing could be valuable in screening patients at high risk of cancer in mass surveys.